Synthesis and Rotational Isomerism of 1‑Substituted Methyl (S)‑[5-(2-Nitrophenyl)‑1H‑pyrazole-4-carbonyl]alaninates

Seven title compounds 12a–g and the (S)-prolinate analogue 13 were prepared in five steps from 2-nitrobenzoic acid (7). Reduction of the nitro group followed by derivatization of the so formed anilines 14 gave the N-alkyl-(15a–c), N-acyl-(16a,b and 19), and N-vinyl derivative 20. NMR spectra of (S)-alanine and (S)-proline derived compounds 12, 13, 14–16, 19, and 20 exhibited two sets of signals corresponding to pairs of conformational diastereomers. The free energy barriers of rotation, ΔG‡298 = 82–86 kJ mol–1, were determined by 1H NMR for 12a, 12d, 12f, and 12g and evaluated by DFT calculations.